SOD function
The FIRST SOD article
Prion protein expression and superoxide dismutase activity
Brown DR, Besinger A
BIOCHEMICAL JOURNAL
334: 423-429 Part 2 SEP 1 1998
Document
type: Article
Language: English
Cited
References: 40
Times
Cited: 98
Explanation
Abstract:
The function of the prion protein (PrPc) remains uncertain. It has been suggested that
prion protein expression may aid cellular resistance to oxidative stress by influencing the
activity of Cu/Zn superoxide dismutase (Cu,Zn SOD), The activity of Cu,Zn SOD was
investigated in mice with different levels of PrPc expression. Increasing levels of PrPc
expression were linked to increased levels of Cu,Zn SOD activity. Western-blot and
Northern-blot analysis indicated that mice either lacking or overexpressing PrPc had
levels of Cu,Zn SOD mRNA equivalent to those expressed in Mild-type mice. Mice
overexpressing the prion protein had lower levels of resistance to oxidative stress but
higher expression levels of glutathione peroxidase, probably due to increased levels of
hydrogen peroxide produced by increased Cu,Zn SOD activity. When cells were
metabolically labelled with radioactive copper, increased radioactivity was
immunoprecipitated with Cu,Zn SOD from mice with higher levels of PrPc. In addition,
diethyldithiocarbamate, a copper chelator that inactivates Cu,Zn SOD by capturing
copper from the molecule, is more able to inactivate Cu,Zn SOD expressed in animals
with higher levels of PrPc. As recent studies have suggested that PrPc may regulate some
aspect of copper metabolism it is suggested that PrPc expression may regulate Cu,Zn
SOD activity by influencing copper incorporation into the molecule.
KeyWords Plus:
Normal prion protein has an activity like that of superoxide dismutase
Brown DR, Wong BS, Hafiz F, Clive C, Haswell SJ, Jones IM
BIOCHEMICAL JOURNAL
344: 1-5 Part 1 NOV 15 1999
Document
type: Article
Language: English
Cited
References: 31
Times
Cited: 155
Explanation
Abstract:
We show here that mouse prion protein (PrPC) either as recombinant protein or
immunoprecipitated from brain tissue has superoxide dismutase (SOD) activity. SOD
activity was also associated with recombinant chicken PrPC confirming the evolutionary
conserved phenotype suggested by sequence similarity. Acquisition of copper by PrPC
during protein folding endowed SOD activity on the protein but the addition of copper
following refolding did not. PrPC dependent SOD activity was abolished by deletion of
the octapeptide-repeat region involved in copper binding. These results describe an
enzymic function for PrPC consistent with its cellular distribution and suggest it has a
direct role in cellular resistance to oxidative stress.
Author Keywords: